Critical roles of RasGRP1 for invariant NKT cell development.
Published
Journal Article
The invariant NKT (iNKT) cell lineage contains CD4(+) and CD4(-) subsets. The mechanisms that control such subset differentiation and iNKT cell maturation in general have not been fully understood. RasGRP1, a guanine nucleotide exchange factor for TCR-induced activation of the Ras-ERK1/2 pathway, is critical for conventional αβ T cell development but dispensable for generating regulatory T cells. Its role in iNKT cells has been unknown. In this study, we report severe decreases of iNKT cells in RasGRP1(-/-) mice through cell intrinsic mechanisms. In the remaining iNKT cells in RasGRP1(-/-) mice, there is a selective absence of the CD4(+) subset. Furthermore, RasGRP1(-/-) iNKT cells are defective in TCR-induced proliferation in vitro. These observations establish that RasGRP1 is not only important for early iNKT cell development but also for the generation/maintenance of the CD4(+) iNKT cells. Our data provide genetic evidence that the CD4(+) and CD4(-) iNKT cells are distinct sublineages with differential signaling requirements for their development.
Full Text
Duke Authors
Cited Authors
- Shen, S; Chen, Y; Gorentla, BK; Lu, J; Stone, JC; Zhong, X-P
Published Date
- November 1, 2011
Published In
Volume / Issue
- 187 / 9
Start / End Page
- 4467 - 4473
PubMed ID
- 21957144
Pubmed Central ID
- 21957144
Electronic International Standard Serial Number (EISSN)
- 1550-6606
Digital Object Identifier (DOI)
- 10.4049/jimmunol.1003798
Language
- eng
Conference Location
- United States